A Protic Ionic Liquid Catalyzes CO2 Conversion at Atmospheric Pressure and Room Temperature: Synthesis of Quinazoline‐2,4(1H,3H)‐diones

The chemical fixation of CO₂ under mild reaction conditions is of significance from a sustainable chemistry viewpoint. Herein a CO₂‐reactive protic ionic liquid (PIL), [HDBU⁺][TFE^?], was designed by neutralization of the superbase 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU) with a weak proton donor trifluoroethanol (TFE). As a bifunctional catalyst for simultaneously activating CO₂ and the substrate, this PIL displayed excellent performance in catalyzing the reactions of CO₂ with 2‐aminobenzonitriles at atmospheric pressure and room temperature, thus producing a series of quinazoline‐2,4(1H,3H)‐diones in excellent yields.     

Palladium‐Catalyzed Migratory Insertion of Isocyanides: An Emerging Platform in Cross‐Coupling Chemistry

Isocyanides have been important building blocks in organic synthesis since the discovery of the Ugi reaction and related isocyanide‐based multicomponent reactions. In the past decade isocyanides have found a new application as versatile C₁ building blocks in palladium catalysis. Palladium‐catalyzed reactions involving isocyanide insertion offer a vast potential for the synthesis of nitrogen‐containing fine chemicals. This Minireview discusses all the achievements in this emerging field.     

Palladium‐Catalyzed [3+3] Annulation between Diarylamines and α,β‐Unsaturated Acids through CH Activation: Direct Access to 4‐Substituted 2‐Quinolinones

A C?H activation strategy has been successfully employed for the high‐yielding synthesis of a diverse array of 4‐substituted 2‐quinolinone species by a palladium‐catalyzed dehydrogenative coupling involving diarylamines. This intermolecular annulation approach incorporates readily available α,β‐unsaturated carboxylic acids as the coupling partner by suppressing the facile decarboxylation. Based on preliminary mechanistic studies, a reaction sequence is proposed, involving ortho palladation, π‐coordination, β‐migratory insertion, and β‐hydride elimination.     

Palladium‐Catalyzed Direct C2 Arylation of N‐Substituted Indoles with 1‐Aryltriazenes

A novel and efficient palladium‐catalyzed C2 arylation of N‐substituted indoles with 1‐aryltriazenes for the synthesis of 2‐arylindoles was developed. In the presence of BF₃ ? OEt₂ and palladium(II) acetate (Pd(OAc)₂), N‐substituted indoles reacted with 1‐aryltriazenes in N,N‐dimethylacetamide (DMAC) to afford the corresponding aryl–indole‐type products in good to excellent yields.     

Palladium‐Catalyzed Aerobic Intermolecular Cyclization of Acrylic Acid with 1‐Octene to Afford α‐Methylene‐γ‐butyrolactones: The Remarkable Effect of Continuous Water Removal from the Reaction Mixture and Analysis of the Reaction by Kinetic,ESI‐MS,and XAFS Measurements

Further study of our aerobic intermolecular cyclization of acrylic acid with 1‐octene to afford α‐methylene‐γ‐butyrolactones, catalyzed by the Pd(OCOCF₃)₂/Cu(OAc)₂ ? H₂O system, has clarified that the accumulation of water generated from oxygen during the reaction causes deactivation of the Cu cocatalyst. This prevents regeneration of the active Pd catalyst and, thus, has a harmful influence on the progress of the cyclization. As a result, both the substrate conversion and product yield are efficiently improved by continuous removal of water from the reaction mixture. Detailed analysis of the kinetic and spectroscopic measurements performed under the condition of continuous water removal demonstrates that the cyclization proceeds in four steps: 1) equilibrium coordination of 1‐octene to the Pd acrylate species, 2) Markovnikov‐type acryloxy palladation of 1‐octene (1,2‐addition), 3) intramolecular carbopalladation, and 4) β‐hydride elimination. Byproduct 2‐acryloxy‐1‐octene is formed by β‐hydride elimination after step 2). These cyclization steps fit the Michaelis–Menten equation well and β‐hydride elimination is considered to be a rate‐limiting step in the formation of the products. Spectroscopic data agree sufficiently with the existence of the intermediates bearing acrylate (Pd? O bond), η³‐C₈H₁₅ (Pd? C bond), or C₁₁H₁₉O₂ (Pd? C bond) moieties on the Pd center as the resting‐state compounds. Furthermore, not only Cu^II, but also Cu^I, species are observed during the reaction time of 2–8 h when the reaction proceeds efficiently. This result suggests that the Cu^II species is partially reduced to the Cu^I species when the active Pd catalytic species are regenerated.     

1‐Bromo‐2‐(cyclopropylidenemethyl)benzene: A Useful Building Block in the Palladium‐Catalyzed Reaction of 2‐Alkynylbenzenamine

A novel palladium‐catalyzed domino reaction of 1‐bromo‐2‐(cyclopropylidenemethyl)benzene and 2‐alkynylbenzenamine is reported, which generates 2‐(naphthalen‐2‐yl)benzenamines and 5H‐indeno[1,2‐c]quinolines via 6‐endo and 5‐exo cyclization, respectively. The regioselectivity for the final outcome can be affected by phosphine and N‐heterocyclic carbene ligands.     

Palladium‐Catalyzed Enantioselective Reductive Heck Reactions: Convenient Access to 3,3‐Disubstituted 2,3‐Dihydrobenzofuran

The first example of highly enantioselective intramolecular hydroarylation of allyl aryl ethers was realized by palladium‐catalyzed reductive heck reactions utilizing a new chiral sulfinamide phosphine ligand (N‐Me‐ XuPhos ). N‐Me‐ XuPhos can be easily prepared on gram scale from readily available starting materials in a one‐pot synthesis approach. A series of optically active 2,3‐dihydrobenzofurans bearing a quaternary stereocenter were obtained in good yields and with excellent enantioselectivities. The practicality of this reaction was validated in the straightforward synthesis of CB2 receptor agonists. Moreover, deuterium was efficiently incorporated into the products.     

Ligand Bite Angle‐Dependent Palladium‐Catalyzed Cyclization of Propargylic Carbonates to 2‐Alkynyl Azacycles or Cyclic Dienamides

The regioselectivity of the palladium‐catalyzed cyclization of propargylic carbonates with sulfonamide nucleophiles is critically dependent on the bite angle of the bidentate phosphine ligand. Ligands with small bite angles favor attack on the central carbon atom of an allenylpalladium intermediate to afford cyclic dienamide products, whereas the use of those with large bite angles leads to alkynyl azacycles, with high stereoselectivity. A computational analysis of the reaction pathway is also presented.     

Palladium‐Catalyzed Multi‐Component Reactions of N‐Tosylhydrazones, 2‐Iodoanilines and CO2 towards 4‐Aryl‐2‐Quinolinones

A palladium‐catalyzed three‐component reaction between N‐tosylhydrazones, 2‐iodoanilines and atmospheric pressure CO₂ was developed whereby a tandem carbene migration insertion/lactamization strategy afforded 4‐aryl‐2‐quinolinones in moderate to good yields. Notably, a wide range of functional groups were tolerated in this procedure. This protocol features the simultaneous formation of four novel bonds; two C?C, one C=C and one C?N (amide), representing an efficient methodology for incorporation of CO₂ into heterocycles.     

Palladium‐Catalyzed C(sp2)−H Alkylation of Aldehyde‐Derived Hydrazones with Functionalized Difluoromethyl Bromides

A palladium‐catalyzed C(sp²)?H difluoromethylation of aldehyde‐derived hydrazones using bromodifluoromethylated compounds to afford the corresponding functionalized difluoromethylketone hydrazones has been established. It is proposed that a radical/SET mechanism proceeding via a difluoroalkyl radical may be involved in the catalytic cycle. Applications of the methodology to the synthesis of α,α‐difluoro‐β‐ketoesters and α,α‐difluoroketones (RCOCF₂H) have been illustrated.     

Palladium‐Catalyzed Asymmetric [4+2] Cycloaddition of 2‐Methylidenetrimethylene Carbonate with Alkenes: Access to Chiral Tetrahydropyran‐Fused Spirocyclic Scaffolds

A palladium‐catalyzed asymmetric [4+2] cycloaddition of 2‐methylidenetrimethylene carbonate with alkenes derived from pyrazolones, indandione, or barbiturate has been successfully developed, affording pharmacologically interesting chiral tetrahydropyran‐fused spirocyclic scaffolds. The target compounds were generated in good to excellent yields and with high enantioselectivity (up to 99 % ee). Furthermore, this cycloaddition reaction could be efficiently scaled up, and several synthetic transformations were accomplished for the construction of other useful chiral spiropyrazolone and spiroindandione derivatives.     

Highly Diastereo‐ and Enantioselective Palladium‐Catalyzed [3+2] Cycloaddition of Vinyl Aziridines and α,β‐Unsaturated Ketones

A palladium‐catalyzed asymmetric [3+2] cycloaddition reaction of vinylaziridines with α,β‐unsaturated ketones, wherein the alkenes have a single activator, is realized in high diastereo‐ and enantioselectivity, thus affording 3,4‐disubstituted pyrrolidines in high yields with excellent ee values. The introduction of a methyl group at C1 of the vinyl group the vinylaziridines greatly improves the stereochemistry of the reaction. A plausible transition state is proposed.